Ixchel M. Brennan

Effects of fat, protein, and carbohydrate and protein load on appetite, plasma cholecystokinin, peptide YY, and ghrelin, and energy intake in lean and obese men

While protein is regarded as the most satiating macronutrient, many studies have employed test meals that had very high and unsustainable protein contents. Furthermore, the comparative responses between lean and obese subjects and the relationships between energy intake suppression and gut hormone release remain unclear. We evaluated the acute effects of meals with modest variations in 1) fat, protein, and carbohydrate content and 2) protein load on gastrointestinal hormones, appetite, and subsequent energy intake in lean and obese subjects. Sixteen lean and sixteen obese men were studied on four occasions. Following a standardized breakfast, they received for lunch: 1) high-fat (HF), 2) high-protein (HP), 3) high-carbohydrate/low-protein (HC/LP), or 4) adequate-protein (AP) isocaloric test meals. Hunger, fullness, and gut hormones were measured throughout, and at t = 180 min energy intake at a buffet meal was quantified. In lean subjects, hunger was less and fullness greater following HF, HP, and AP compared with HC/LP meals, and energy intake was less following HF and HP compared with HC meals (P < 0.05). In the obese subjects, hunger was less following HP compared with HF, HC/LP, and AP meals, and energy intake was less following HP and AP compared with HF and HC meals (P < 0.05). There were no major differences in hormone responses to the meals among subject groups, but the CCK and ghrelin responses to HP and AP were sustained in both groups. In conclusion, HP meals suppress energy intake in lean and obese subjects, an effect potentially mediated by CCK and ghrelin, while obese individuals appear to be less sensitive to the satiating effects of fat.

Effects of the phases of the menstrual cycle on gastric emptying, glycemia, plasma GLP-1 and insulin, and energy intake in healthy lean women

There is evidence that the menstrual cycle affects appetite, such that energy intake is lower during the follicular compared with the luteal phase. Gastric emptying influences energy intake, glycemia, and plasma glucagon-like peptide-1 (GLP-1), insulin, and cholecystokinin (CCK) release. We hypothesized that 1) gastric emptying of a glucose drink is slower, and glycemia, plasma hormones, hunger, and energy intake are less, during the follicular compared with the luteal phase; 2) the reduction in the latter parameters during the follicular phase are related to slower gastric emptying; and 3) these parameters are reproducible when assessed twice within a particular phase of the menstrual cycle. Nine healthy, lean women were studied on three separate occasions: twice during the follicular phase (days 6-12) and once during the luteal phase (days 18-24). Following consumption of a 300-ml glucose drink (0.17 g/ml), gastric emptying, blood glucose, plasma hormone concentrations, and hunger were measured for 90 min, after which energy intake at a buffet meal was quantified. During the follicular phase, gastric emptying was slower (P < 0.05), and blood glucose (P < 0.01), plasma GLP-1 and insulin (P < 0.05), hunger (P < 0.01), and energy intake (P < 0.05) were lower compared with the luteal phase, with no differences for CCK or between the two follicular phase visits. There were inverse relationships between energy intake, blood glucose, and plasma GLP-1 and insulin concentrations with the amount of glucose drink remaining in the stomach at t = 90 min (r < -0.6, P < 0.05). In conclusion, in healthy women 1) gastric emptying of glucose is slower, and glycemia, plasma GLP-1 and insulin, hunger, and energy intake are less during the follicular compared with the luteal phase; 2) energy intake, glycemia, and plasma GLP-1 and insulin are related to gastric emptying; and 3) these parameters are reproducible when assessed twice during the follicular phase.

Intravenous CCK-8, but not GLP-1, suppresses ghrelin and stimulates PYY release in healthy men.

We have investigated the effects of exogenous CCK-8 and GLP-1, alone and in combination, on ghrelin and PYY secretion. Nine healthy males were studied on four occasions. Plasma ghrelin and PYY concentrations were measured during 150 min intravenous infusions of: (i) isotonic saline, (ii) CCK-8 at 1.8 pmol/kg/min, (iii) GLP-1 at 0.9 pmol/kg/min or (iv) CCK-8 and GLP-1 combined. CCK-8 markedly suppressed ghrelin and stimulated PYY when compared with control between t=0-120 min (P<0.001 for both). GLP-1 had no effect on ghrelin, but decreased PYY slightly at 120 min (P<0.05). During infusion of CCK-8+GLP-1, there was comparable suppression of ghrelin (P<0.001), but the stimulation of PYY was less (P<0.001), than that induced by CCK-8, between t=20-120 min. In conclusion, in healthy subjects, in the doses evaluated, exogenous CCK-8 suppresses ghrelin and stimulates PYY, and exogenous GLP-1 has no effect on ghrelin and attenuates the effect of CCK-8 on PYY.

Pooled-data analysis identifies pyloric pressures and plasma cholecystokinin concentrations as major determinants of acute energy intake in healthy, lean men

BACKGROUND The interaction of nutrients with the small intestine modulates gastropyloroduodenal motility, stimulates the release of gut hormones, and suppresses appetite and energy intake. OBJECTIVE We evaluated which, if any, of these variables are independent determinants of acute energy intake in healthy, lean men. DESIGN We pooled data from 8 published studies that involved a total of 67 healthy, lean men in whom antropyloroduodenal pressures, gastrointestinal hormones, and perceptions were measured during intraduodenal nutrient or intravenous hormone infusions. In all of the studies, the energy intake at a buffet lunch was quantified immediately after the infusions. To select specific motor, hormone, or perception variables for inclusion in a multivariable mixed-effects model for determination of independent predictors of energy intake, we assessed all variables for collinearity and determined within-subject correlations between energy intake and these variables by using bivariate analyses adjusted for repeated measures. RESULTS Although correlations were shown between energy intake and antropyloroduodenal pressures, plasma hormone concentrations, and gastrointestinal perceptions, only the peak number of isolated pyloric-pressure waves, peak plasma cholecystokinin concentration, and area under the curve of nausea were identified as independent predictors of energy intake (all P < 0.05), so that increases of 1 pressure wave, 1 pmol/L, and 1 mm . min were associated with reductions in energy intake of approximately 36, approximately 88, and approximately 0.4, respectively. CONCLUSION We identified specific changes in gastrointestinal motor and hormone functions (ie, stimulation of pyloric pressures and plasma cholecystokinin) and nausea that are associated with the suppression of acute energy intake.

Gastric emptying, mouth-to-cecum transit, and glycemic, insulin, incretin, and energy intake responses to a mixed-nutrient liquid in lean, overweight, and obese males

Observations relating to the impact of obesity on gastric emptying (GE) and the secretion of gut hormones are inconsistent, probably because of a lack of studies in which GE, gastrointestinal hormone release, and energy intake (EI) have been evaluated concurrently with previous patterns of nutrient intake. GE is known to be a major determinant of postprandial glycemia and incretin secretion in health and type 2 diabetes. The aims of this study were to determine the effects of a mixed-nutrient drink on GE, oro-cecal transit, blood glucose, insulin and incretin concentrations and EI, and the relationship between the glycemic response to the drink with GE in lean, overweight, and obese subjects. Twenty lean, 20 overweight, and 20 obese males had measurements of GE, oro-cecal transit, and blood glucose, insulin, GLP-1, and GIP concentrations for 5 h after ingestion of a mixed-nutrient drink (500 ml, 532 kcal); EI at a subsequent buffet lunch was determined. Habitual EI was also quantified. Glycemic and insulinemic responses to the drink were greater in the obese (both P < 0.05) when compared with both lean and overweight, with no significant differences in GE, intragastric distribution, oro-cecal transit, incretins, or EI (buffet lunch or habitual) between groups. The magnitude of the rise in blood glucose after the drink was greater when GE was relatively more rapid (r = -0.55, P < 0.05). In conclusion, in the absence of differences in habitual EI, both GE and incretin hormones are unaffected in the obese despite greater glucose and insulin responses, and GE is a determinant of postprandial glycemia.

Effects of varying combinations of intraduodenal lipid and carbohydrate on antropyloroduodenal motility, hormone release, and appetite in healthy males

Intraduodenal infusions of both lipid and glucose modulate antropyloroduodenal motility and stimulate plasma CCK, with lipid being more potent than glucose. Both stimulate glucagon-like peptide-1, but only lipid stimulates peptide YY (PYY), while only glucose raises blood glucose and stimulates insulin. When administered in combination, lipid and carbohydrate may, thus, have additive effects on energy intake. However, elevated blood glucose levels do not suppress energy intake, and the effect of insulin is controversial. We hypothesized that increasing the ratio of maltodextrin, a complex carbohydrate, relative to lipid would be associated with a reduction in effects on antropyloroduodenal pressures, gut hormones, appetite, and energy intake, when compared with lipid alone. Ten healthy males were studied on three occasions in double-blind, randomized order. Antropyloroduodenal pressures, plasma CCK, PYY and insulin, blood glucose, and appetite were measured during 90-min intraduodenal infusions of 1) 3 kcal/min lipid (L3), 2) 2 kcal/min lipid and 1 kcal/min maltodextrin (L2/CHO1), or 3) 1 kcal/min lipid and 2 kcal/min maltodextrin (L1/CHO2). Energy intake at a buffet lunch consumed immediately after the infusion was quantified. Reducing the lipid (thus, increasing the carbohydrate) content of the infusion was associated with reduced stimulation of basal pyloric pressures (r = 0.76, P < 0.01), plasma CCK (r = 0.66, P < 0.01), and PYY (r = 0.98, P < 0.001), and reduced suppression of antral (r = -0.64, P < 0.05) and duodenal (r = -0.69, P < 0.05) pressure waves, desire-to-eat (r = -0.8, P < 0.001), and energy intake (r = 0.74, P < 0.01), with no differences in phasic (isolated) pyloric pressures. In conclusion, in healthy males, intraduodenal lipid is a more potent modulator of gut function, associated with greater suppression of energy intake, when compared with isocaloric combinations of lipid and maltodextrin.

Effects of acute dietary restriction on gut motor, hormone and energy intake responses to duodenal fat in obese men

Background:Previous patterns of energy intake influence gastrointestinal function and appetite, probably reflecting changes in small-intestinal nutrient-mediated feedback. Obese individuals consume more fat and may be less sensitive to its gastrointestinal and appetite-suppressant effects than lean individuals.Objective:To evaluate the hypothesis that, in obese individuals, the effects of duodenal fat on gastrointestinal motor and hormone function, and appetite would be enhanced by a short period on a very-low-calorie diet (VLCD).Methods:Eight obese men (body mass index 34±0.6 kg m−2) were studied on two occasions, before (V1), and immediately after (V2), a 4-day VLCD. On both occasions, antropyloroduodenal motility, plasma cholecystokinin (CCK), peptide-YY (PYY) and ghrelin concentrations, and appetite perceptions were measured during a 120-min intraduodenal fat infusion (2.86 kcal min−1). Immediately afterwards, energy intake was quantified.Results:During V2, basal pyloric pressure and the number and amplitude of isolated pyloric pressure waves (PWs) were greater, whereas the number of antral and duodenal PWs was less, compared with V1 (all P<0.05). Moreover, during V2, baseline ghrelin concentration was higher; the stimulation of PYY and suppression of ghrelin by lipid were greater, with no difference in CCK concentration; and hunger and energy intake (kJ; V1: 4378±691, V2: 3634±700) were less (all P<0.05), compared with V1.Conclusions:In obese males, the effects of small-intestinal lipid on gastrointestinal motility and some hormone responses and appetite are enhanced after a 4-day VLCD.

Effect of small intestinal glucose load on plasma ghrelin in healthy men

Postprandial ghrelin suppression arises from the interaction of meal contents with the small intestine and may relate to elevations in blood glucose and/or plasma insulin. We sought to determine whether the suppression of ghrelin by small intestinal glucose is dependent on the glucose load and can be accounted for by changes in blood glucose and/or plasma insulin. Blood glucose, plasma insulin, and plasma ghrelin levels were measured in 10 healthy males (aged 32+/-4 yr; body mass index: 25.1+/-0.4 kg/m2) during intraduodenal glucose infusions at 1 kcal/min (G1), 2 kcal/min (G2), and 4 kcal/min (G4), as well as intraduodenal hypertonic saline (control) for 120 min. There was a progressive decrease in ghrelin with all treatments, control at 45 min and between 90 and 120 min (P<0.05) and G1 (P<0.05), G2 (P<0.0001), and G4 (P<0.0001) between 30 and 120 min to reach a plateau at approximately 90 min. There was no difference in plasma ghrelin between G1, G2, or G4. Control suppressed ghrelin to a lesser extent than intraduodenal glucose (P<0.05). The suppression of ghrelin was not related to rises in blood glucose or plasma insulin. Suppression of ghrelin by intraduodenal glucose in healthy males is apparently independent of the glucose load and unrelated to blood glucose or insulin levels.

S2095c Gastric Emptying Is Slower, and Hunger and Energy Intake Are Less, Pre-Ovulation When Compared with Post-Ovulation in Healthy Lean Women

BACKGROUND: There is evidence that the menstrual cycle affects appetite, such that energy intake is lower pre-ovulation than post-ovulation (Li et al, Appetite 1999; 33:109-118). Since changes in gastric emptying (GE) contribute to acute energy intake, an understanding of how the menstrual cycle affects GE is important. Furthermore, knowledge on day-to-day variations in energy intake, i.e. within the same phase of the menstrual cycle, is limited. AIMS: To assess the hypotheses that (i) GE is slower, and hunger and energy intake are less, pre-ovulation than post-ovulation, (ii) GE and energy intake are reproducible when assessed twice within a particular phase of the menstrual cycle (eg pre-ovulation) and (iii) the reduction in hunger and energy intake pre-ovulation will be related to slower GE. METHODS: 9 healthy, lean females (aged 32±1 years; BMI: 21.6±0.5 kg/m2) were studied on 3 separate occasions; twice pre-ovulation (between days 6-12; “Pre-V1” and “Pre-V2”), and once post-ovulation (between days 18-24; “Post”). Visits were randomized in singleblind fashion over consecutive menstrual cycles. Following consumption of a 300 ml glucose drink (815 kJ), GE (using 3D ultrasound) and hunger (using visual analogue scales) were measured for 90 min. Between 90-120 min, energy intake at a buffet meal was quantified. RESULTS: During pre-ovulation, GE was slower (P<0.05) (Figure A), while hunger (P<0.01) and energy intake (P<0.05) were less (Figure B), when compared with post-ovulation. There were no differences in any of the parameters between the two pre-ovulation visits. There were inverse relationships between both scores for hunger immediately before the buffet meal and energy intake with GE (AUC) (r= -0.5, P<0.05 for both). CONCLUSIONS: Hunger and energy intake are lower pre-ovulation and associated with slower GE when compared with post-ovulation. Furthermore, there are no differences between these parameters when assessed twice during pre-ovulation. Taken together, the phase of the menstrual cycle should be controlled for when evaluating gastrointestinal function and energy intake in female volunteers.